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Chi-Med Initiates a Phase I Trial of IDH1/2 Dual Inhibitor in Patients with Hematological Malignancies in China

Hong Kong, Shanghai & Florham Park, NJ: Friday, July 24, 2020: Hutchison China MediTech Limited (“Chi-Med”) (Nasdaq/AIM: HCM) has initiated a Phase I study of HMPL-306, its novel selective small molecule dual inhibitor of isocitrate dehydrogenase (“IDH”) 1 and 2 mutations, in patients with hematological malignancies in China.  The first patient was dosed today.


This is a multi-center study to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL‑306 in patients of relapsed or refractory hematological malignancies with an IDH1 and/or IDH2 mutation.  The first stage of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of HMPL‑306 to determine the maximum tolerated dose and/or the recommended Phase II dose (“RP2D”).  The second stage of the study is a dose expansion phase where three cohorts of patients will receive HMPL‑306 to further evaluate the safety, tolerability, and clinical activity at the RP2D.  Additional details may be found at, using identifier NCT04272957.


HMPL-306 is Chi-Med’s ninth innovative oncology asset discovered in house.  Cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 have been known to switch to the other form when targeted by an inhibitor of IDH1 mutant alone or IDH2 mutant alone.  By targeting both IDH1 and IDH2 mutations, this drug candidate may provide therapeutic benefits in cancer patients harboring IDH mutations, and may address acquired resistance to IDH inhibition through isoform switching. 



About IDH and Hematological Malignancies


IDHs are critical metabolic enzymes that help to break down nutrients and generate energy for cells.  When mutated, IDH creates a molecule that alters the cell’s genetic programming and prevents cells from maturing.  IDH1 or IDH2 mutations are common genetic alterations in various types of blood and solid tumors, including acute myeloid leukemia (“AML”) with approximately 20% of patients having mutant IDH genes, myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), low-grade glioma and intrahepatic cholangiocarcinoma.  Mutant IDH isoform switching, either from cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice versa, is a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma.[i],[ii],[iii]


According to the National Cancer Institute (NCI), there will be approximately 20,000 new cases of AML in the U.S. in 2020 and the five-year relative survival rate is 28.7%[iv].  Currently, the U.S. Food and Drug Administration (FDA) has approved one drug for IDH1 mutation and one drug for IDH2 mutation, but no dual inhibitor targeting both IDH1 and IDH2 mutants has been approved.  There were an estimated 19,700 new cases of AML in China in 2018 and is estimated to reach 24,200 in China in 2030.[v]  In China no IDH inhibitor has been approved.



About Chi-Med


Chi-Med (Nasdaq/AIM: HCM) is an innovative biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases.  It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit:

[i]    S Choe S et al. Blood 2019;134(Supplement_1):545. doi:10.1182/blood-2019-122671.

[ii]   Harding JJ et al. Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition. Cancer Discov. 2018;8(12):1540-1547. doi:10.1158/2159-8290.CD-18-0877.

[iii] Delahousse J et al. Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase-mutated intrahepatic cholangiocarcinomas. Eur J Cancer. 2018;90:83-91. doi:10.1016/j.ejca.2017.11.024.

[iv]   Source: National Cancer Institute –

[v]   Lin J et al. IDH1 and IDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol. 2012;91(4):519-525. doi:10.1007/s00277-011-1352-7.

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  • Company:
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    • Hutchison China MediTech Limited
Last Updated: 24-Jul-2020